Severe emphysema is a debilitating disease that limits the quality of life of patients and represents an end state of Chronic Obstructive Pulmonary Disease (COPD). It is believed that 3.5 million people in the US have the severe emphysematous form of COPD, and it is increasing in both prevalence and mortality. Current treatment methods for severe emphysema include lung volume reduction (LVR) surgery, which is highly invasive and can be risky and uncomfortable for the patient. New treatment methods for treating emphysema include bronchoscopy guided lung volume reduction devices that aim to close off ventilation to the diseased regions of the lung but maintain ventilation to healthier lung. However, the complex three dimensional structure of the lungs and the diversity of COPD within the lungs of an individual patient makes understanding the disease within each patient difficult.
There are at least two phenotypes of COPD, emphysema and airway obstruction, which is also referred to as air trapping or small airway disease. Emphysema occurs when the lung parenchyma is gradually destroyed, resulting in a loss of elasticity. Small airway disease, in contrast, is characterized by airway inflammation and remodeling, which can lead to airway obstruction and the trapping of gas within the lung. In many patients, COPD progresses from small airway disease to emphysema, which typically includes air trapping as well as a loss of elasticity. In addition, both phenotypes may be present in different portions of a patient's lungs. Understanding and differentiating these two phenotypes is important for understanding the disease process and for selecting treatment for patients.
Currently, airway limitation can be diagnosed by spirometry and is graded into 5 stages according to the Global Initiative for Chronic Obstructive Lung Diseases (GOLD) criteria. In addition, CT images, may be used to characterize the lungs by measuring the Hounsfield Unit (HU) of the CT images at full inspiration and full expiration. Emphysema is diagnosed if the HU is less than −950 in a full inspiration CT scan. Air trapping is diagnosed if the HU is less than −856 HU in an end-expiration or residual volume CT scan. This analysis may be determined using the entire lung, or to a limited extent may be based on different portions of the lung, to identify the presence of emphysema or air trapping in particular portions of the lung. However, because of the dynamic nature of the lung due to the expansion that occurs during breathing, assessment of the presence of COPD by this method using one static image is limited. To overcome this, some measurements have been derived from the pair of inspiration and expiration scans, such as the ratio of mean lung density between expiration and inspiration (E/I ratio) and relative volume changes (RVC) between −850 HU to −950 HU, and they have shown better correlations against clinical metadata. In addition, to further improve upon the methods of CT diagnosis of emphysema and small airway disease in particular locations in the lung, researchers have recently published a method which includes registering (matching) inspiration and expiration CT scans. In particular, like the prior art CT method described above, one method uses defined cut-off values for determining whether emphysema or small airway disease is present at matched locations. An example of such as method has been described by Galban et al., CT-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression,” Nat. Med., vol. 18, no. 11, pp. 1711-5, November 2012. However, this approach still has limitations.
Another lung disease, lung cancer, is the world's leading cause of cancer death, with more annual deaths (approximately 28% of all cancer deaths) than any other cancers which have routine screening programs such as breast, colorectal and prostate. In 2013, the U.S. mortality rate was 160,340 persons (approximately 28% of all cancer deaths), and an estimated 3,400 lung cancer deaths were among non-smokers caused by exposure to secondhand smoke.
Currently in the U.S., there are 373,489 persons diagnosed with lung cancer with an incidence rate of 226,160 new diagnoses each year (˜14% of all cancer diagnoses). However, only 15% of lung cancer cases are diagnosed at an early stage; thus, 85% of diagnosed lung cancer is late stage. For patients diagnosed with lung cancer, there is only 16.3% five-year survival rate. This is much lower than many of the other leading cancers, such as colon (65.2%), breast (90.0%) and prostate (99.9%). The five-year survival rate is much higher in cases where the cancer is detected and localized within the lungs (52.6%), whereas if the cancer has metastasized to other organs, the five-year survival is only 3.5%. Of those diagnosed with lung cancer, over half die within the first year of diagnosis. Early diagnosis is therefore imperative.
CT imaging is also useful for lung cancer screening, and is becoming accepted for patients at high risk of developing lung cancer. These include patients aged 55 to 80 years with a smoking history of 30 pack-year of more who currently smoke or have quit smoking within the past 15 years. However, even among these high risk individuals, some individuals may be more likely to develop lung cancer than others. If additional risk factors could be determined, this would be useful for developing a more refined approach to cancer screening. In this way, the use of expensive CT scans, with the inherent dosing of radiation and the risk of false positive results, could be adjusted according to a more individualized risk analysis.